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Category: genetics – Page 4

CRISPR roadblocks: Scientists identify genes blocking gene therapy success

Like a delivery driver navigating crowded city streets, a gene-therapy-toting lipid nanoparticle faces a gauntlet of potential detours on its journey toward a cell’s nucleus. First, there’s entering the cell’s plasma membrane; then navigating around organelles like the Golgi apparatus, mitochondria and endoplasmic reticulum—all destinations that can errantly absorb the particle’s payload, rendering it ineffective at best or harmful at worst. And that’s all before the particle even enters the nucleus and successfully makes a genetic change.

Sleep could help identify people at risk of developing Alzheimer’s disease at an earlier stage

What if certain signs of the disease were to manifest subtly during sleep, long before the first memory problems appear? This is the line of inquiry being explored by a team of researchers at ULiège.

A team of scientists from the University of Liège (GIGA Neurosciences), supported by the Stop Alzheimer’s Foundation, has analyzed the sleep patterns of more than 500 healthy people. Among middle-aged participants, a higher frequency of nocturnal micro-awakenings was found to be associated with a greater genetic risk of developing Alzheimer’s disease, whereas this link was not observed in young adults. This research, published in the journal Sleep, suggests that the study of sleep could, in the long term, contribute to the early identification of vulnerable individuals.

Glioblastoma isoform diversity mapping

Researchers have achieved a major breakthrough in brain cancer research by developing the most comprehensive map to date of isoform diversity in glioblastoma, the most common and aggressive form of brain cancer in adults. Using advanced long-read single-cell sequencing, the team uncovered thousands of previously unknown tumor-specific genetic isoforms that had remained invisible to conventional approaches. The discovery reveals a new source of potential therapeutic targets, including candidates that could be harnessed for future personalised cancer vaccines and immunotherapies. The findings were published in Nature Communications.

Glioblastoma is notoriously difficult to treat because tumor cells within the same patient can behave, grow and respond to treatment differently. Understanding this cellular diversity is essential for developing more effective therapies.

Every gene in the human body can produce slightly different versions of its genetic instructions, known as isoforms. These variations can profoundly influence cellular function and in cancer, may determine whether tumour cells are recognised by the immune system or evade detection. Until now, the technology used to study individual cancer cells could read only short fragments of genetic information, limiting researchers’ ability to study full-length isoforms in individual cells.

In vivo CRISPR screen identifies gene edits that strengthen CAR-T therapy against solid tumors

For patients with blood cancers like leukemia and lymphoma, the immunotherapy known as CAR-T cell therapy can be lifesaving. Doctors remove a patient’s immune cells, called T cells, engineer them in the lab to better recognize and attack cancer, and infuse them back into the bloodstream. But for solid tumors—which include lung, pancreatic, ovarian, colon, breast and other cancer types—these engineered immune cells still face too much resistance to effectively treat the disease.

Now, scientists at Gladstone Institutes and UC San Francisco (UCSF) have discovered a pair of genetic edits that make CAR-T cells more effective at infiltrating and fighting solid tumors. In mice, T cells with these edits dramatically outperformed standard CAR-T cells, clearing tumors in many cases where unedited CAR-T cells had little or no effect.

The discovery, published in Nature, was made using the world’s first in vivo genome-wide CRISPR screen in human T cells. Developed by the same team, this platform enabled researchers to study the effects of gene edits on CAR-T cells inside living mice across the entire genome, rather than only in isolated cell cultures in a dish.

Genetic switch could help tomatoes produce fruit in cold weather

Every tomato begins with a flower. But before a fruit can grow, an intricate sequence of events must happen in perfect order. The flower’s male and female organs must develop together, pollen must be released at exactly the right time, and fertilization must occur.

Many things can disrupt this delicate process, including genetic changes and environmental stress. Temperature extremes are a major challenge: Cold can reduce pollen viability and prevent fertilization, while previous research has shown that heat can also interfere with fruit set.

Now, researchers have uncovered a genetic system that keeps this process synchronized. Their findings could eventually help scientists develop tomato varieties that produce fruit more reliably during challenging growing conditions, including colder seasons.

Did Cellular Life Begin Twice? New Study Points to Two Independent Origins

Early metabolism may have begun as a mix of metal and enzyme catalysis before bacteria and archaea independently evolved into free-living cells.

Four billion years ago, the chemistry that eventually became life may have been unfolding around hydrothermal vents, where naturally occurring metals helped drive reactions before cells possessed the full machinery they use today. Researchers at Heinrich Heine University Düsseldorf (HHU) and collaborating institutions have reconstructed part of that transition, tracing how metabolism and enzymes changed as the ancestors of bacteria and archaea began to diverge.

The study, published in Science Advances, examined the chemical network early cells used to produce essential components of life and investigated how those reactions could have been powered. The researchers conclude that the transition to free-living bacteria and archaea may have occurred independently, even though both lineages share the same underlying genetic code.

Genome study reveals centromeres as one of the fastest-changing regions in human DNA

A centromere is a specific region on a chromosome that ensures that, when a cell divides, the chromosome separates accurately so each new cell receives the correct amount of genetic material. Despite their essential role, centromeres remain one of the last major blind spots in the human genome.

A recent study published in Nature set out to reveal what had been hidden inside human centromeres, using advanced long-read sequencing and custom-built computational tools to piece together 2,110 complete centromeres. The researchers sampled individuals from 28 population groups across five continents, then compared their centromeres with 5,747 assembled by the Human Pangenome Reference Consortium to trace how these regions differ and evolve.

They discovered 226 major centromere haplotypes—distinct genetic patterns—and 1,870 new genetic variants. By studying a four-generation family, they were able to follow centromeres as they changed from parent to child, tracking genetic changes across generations.

For 15,000 years, humans and dogs have been changing each other

Dogs have been shaping—and being shaped by—humans for about 15,000 years, evolving from early partners of hunter-gatherers into an astonishing range of specialized companions. Across the globe, they adapted alongside people to wildly different environments and needs, from powerful Arctic sled dogs and agile rainforest hunters to high-altitude dogs with genetic traits for surviving thin air. Some were even bred for wool, while others played important spiritual or ceremonial roles.

Molecular structures provide roadmap for targeted Parkinson’s disease therapeutics

Researchers at Weill Cornell Medicine have uncovered how a key Parkinson’s protein called LRRK2 shifts between inactive and active forms, revealing the structural changes that enable certain mutations to push the protein into an overactive state. Mutations that cause LRRK2 to become abnormally active are among the most common genetic causes of Parkinson’s disease. Even without these mutations, some people with Parkinson’s disease have elevated LRRK2 activity.

Understanding exactly how LRRK2 becomes overactive has become increasingly important because it is one of the leading targets for developing treatments that could slow Parkinson’s disease.

Using electron microscopy and biochemistry, the team captured the structure of LRRK2 in different states, enabling them to elucidate how the protein toggles between active and inactive forms. The findings, published in Cell, point toward a new generation of targeted therapies.

DNA repair enzymes favor specific sequences, shaping mutation patterns in the human genome

When a wound does not heal properly, it leaves a scar. Similarly, mutations—which are permanent changes to genetic code—are often the result of damaged DNA that has not been properly repaired. Mutations can impede the function of genes and lead to disease and aging, but they are also the source of genetic variation, which allows new traits to emerge and facilitates the evolutionary process. Scientists still do not fully understand why some damaged DNA segments are successfully repaired while others are not.

In a new study published in Nature Communications, researchers from the Weizmann Institute of Science succeeded in identifying which DNA sequences and structures are the preferred targets for several of the most important DNA repair enzymes. The findings from the laboratory of Dr. Ariel Afek suggest that these preferences shaped the human genome and could even help explain how cells become cancerous.

Every day, thousands of chemical reactions take place in every living cell, damaging the genome. “When DNA repair systems work properly, they repair most of the damage, but not all of it,” Afek explains. “Therefore, the rate at which mutations accumulate is a balance between the rate of damage and the rate of repair.

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